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Formulation of cinnarizine for stabilization of its physiologically generated supersaturation

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posted on 2023-06-07, 06:30 authored by Maryam Maghsoodi, Ali Nokhodchi, Mahzad Azhdarzadeh Oskuei, Saman Heidari
Physiologically generated supersaturation and subsequent crystallization of a weakly basic drug in the small intestine leads to compromised bioavailability. In this study, the pH-induced crystallization of cinnarizine (CNZ) in the presence of different polymers was investigated. Inhibitory effect of Eudragit L100 (Eu) on crystallization of CNZ at varying supersaturation ratios was examined. The effect of Eu on the dissolution behavior of CNZ from CNZ/Eu physical mixtures (PMs) and solid dispersions (SDs) was assessed. Results showed that both Eu and hydroxypropyl methylcellulose (HPMC) have a considerable maintenance effect on supersaturation of CNZ but Eu was more effective than HPMC. When Eudragit was used the phenomenon of liquid-liquid phase separation (formation of colloidal phase) was observed at supersaturation ratio of 20 times above the solubility of the drug. PMs showed a higher area under the dissolution curve (AUDC) compared with plain CNZ. In contrast, SDs showed a lower AUDC than plain CNZ. For SDs, the AUDC was limited by the slow release of the drug from Eu in acidic pH which in turn hindered the creation of CNZ supersaturation following the transition of acidic to neutral pH. From these findings, it can be concluded that the ability of the formulation to generate supersaturation state and also maintain the supersaturation is vital for improving the dissolution of CNZ. supersaturation following the transition of acidic to neutral pH. From these findings, it can be concluded that the ability of the formulation to generate supersaturation state and also maintain the supersaturation is vital for improving the dissolution of CNZ.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

AAPS PharmSciTech

ISSN

1530-9932

Publisher

American Association of Pharmaceutical Scientists

Issue

3

Volume

20

Page range

139 1-11

Department affiliated with

  • Chemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2019-04-03

First Open Access (FOA) Date

2020-03-11

First Compliant Deposit (FCD) Date

2019-04-02

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